Abstract The gastrointestinal tract harbors one of the highest densities of microorganisms on Earth. This collection of microbial genomes is an extension to the human genome, with clear implications on human health and disease. Early events in microbial colonization have a profound effect on physiology and immune education in the gut, thereby impacting disease susceptibility (including obesity, asthma, and other inflammatory disorders later in life). The human gut microbiota colonizes, stabilizes, and matures during the first few years of life, yet we know remarkably little about the natural history of how the microbiome forms in children. The study proposed here will provide fundamental knowledge about the newborn gut microbiome ? including its establishment; response to nutrients; and its implication for disease. This project aims to understand how maternal factors shape infant gut microbiome development and how early life microbial composition influence the allergy onset. Using newly established and future prospective birth cohorts, we will undertake metagenomic sequencing, strain-level analysis and bacterial isolation and characterization. (1) We will identify how delivery mode affects the abundant strains in the newborn gut, along with their potential parental sources. (2) We will isolate bacteria from newborn guts and determine if there is a personalized match between mother's breast milk and her child's gut microbiome. (3) We will examine the influence of the infant gut microbiome and early feeding on allergy to cow's milk. This research will illuminate how environmental factors modulate infant gut colonization and how the gut microbiota affect the onset of pediatric allergies. This will serve as a basis for the development of evidence- based interventions to colonize the gut of children born by C-section; supplement the diet of formula-fed children; and shift the infant gut microbiome to a less ?allergy-prone? state.